title: Pharmacophore-based virtual screening and Bayesian model for the identification of potential human leukotriene A4 hydrolase inhibitors.
abstract: Leukotriene A4 hydrolase (LTA4H), an enzyme involved in the conversion of LTA4 to LTB4, is an emerging and important anti-inflammatory target. This study demonstrates the development of quantitative pharmacophore hypothesis and Bayesian model and their applications in identification of potential human LTA4H (hLTA4H) inhibitors. The best hypothesis with a high correlation coefficient value of 0.951 was validated using different methods including a test set containing 136 compounds. It was further used as a three-dimensional query in database searching to retrieve virtual leads for hLTA4H inhibition. Molecular docking study was employed to identify the compounds that bind the active site with high affinity. Developed Bayesian model suggested molecular features favoring and not favoring the inhibition of hLTA4H.
authors.affiliation: Division of Applied Life Science (BK21 Program), Environmental Biotechnology National Core Research Center (EB-NCRC), Gyeongsang National University (GNU), 900 Gazwa-dong, Jinju 660-701, Republic of Korea.
authors.forename: Sundarapandian
authors.initials: S
authors.lastname: Thangapandian
authors.forename: Shalini
authors.initials: S
authors.lastname: John
authors.forename: Sugunadevi
authors.initials: S
authors.lastname: Sakkiah
authors.forename: Keun Woo
authors.initials: KW
authors.lastname: Lee
mesh_terms: D001499:Bayes Theorem; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D057166:High-Throughput Screening Assays; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase